Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2)

Kavanaugh, Arthur; Puig, Lluís; Gottlieb, Alice B.; Ritchlin, Christopher T.; Yin, You; Li, Shu; Song, Michael; Randazzo, B.; Rahman, Proton; McInnes, Iain B.

doi:10.1136/annrheumdis-2015-209068

Cited by 140 publications

(80 citation statements)

References 21 publications

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“…It has also shown benefit in AS in an open-label study30 and a separate post hoc pooled analysis 31. Intriguingly, and in direct contrast to IL-17A blockade, ustekinumab is effective in CD with evidence for a prolonged benefit following a single infusion 32 33.…”

Section: The Th17 Axismentioning

confidence: 99%

Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

2017

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The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.

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Section: The Th17 Axismentioning

confidence: 99%

Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

2017

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“…Additional composite measures, determined post hoc employing component data available from preplanned study assessments, included the Psoriatic ArthritiS Disease Activity Score (PASDAS), the Disease Activity in Psoriatic Arthritis (DAPsA) score, and the Clinical Disease Activity Index (CDAI). The PASDAS [20,21] was calculated using patient global disease activity VAS (arthritis and psoriasis), physician global disease activity VAS, 68-joint TJC, 66-joint SJC, CRP, enthesitis (LEI), dactylitis (scores of 0-3 recoded to 0-1, where any score > 0 equaled 1; range, 0-20) [22], and the physical component summary score of the 36-item Short Form Health Survey [23]. Disease activity cutoffs were remission (≤ 1.9), low (> 1.9-< 3.2), moderate (≥ 3.2-< 5.4), and high (≥ 5.4) [24].…”

Section: Clinical Assessments and Composite Endpointsmentioning

confidence: 99%

Inhibition of radiographic progression across levels of composite index-defined disease activity in patients with active psoriatic arthritis treated with intravenous golimumab: results from a phase-3, double-blind, placebo-controlled trial

et al. 2020

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Background: In the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment.Methods: In this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2 mg/kg (N = 241; week 0, week 4, every 8 weeks [q8w]) or placebo (N = 239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed. Results: Across indices, golimumab-treated patients demonstrated less radiographic progression than placebotreated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were − 0.83 vs. 0.91, respectively, in patients achieving MDA and − 0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placeborandomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab-vs. placebo→golimumab-treated patients achieving MDA were − 1.16 vs.

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“…Inhibition of IL-12 and IL-23 leads to an inhibition of Th1 and Th17 T‑cells leads to an inhibition of important inflammatory pathways in PsA [36]. In phase 3 trials ustekinumab especially showed improvement in skin disease but other factors, such as enthesitis, dactylitis, nail disease, physical function and quality of life also improve [42]. Another new therapeutic agent is secukinumab, a human monoclonal IgG1k antibody, targeting IL-17A, which also has a proinflammatory role in the pathophysiology of PsA.…”

Section: Novel Treatment Targetsmentioning

confidence: 99%

An overview of psoriatic arthritis – epidemiology, clinical features, pathophysiology and novel treatment targets

Kerschbaumer

Fenzl²,

Erlacher³

et al. 2016

Wien Klin Wochenschr

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SummaryPsoriatic arthritis is a chronic inflammatory joint disease occurring in a subgroup of patients suffering from psoriasis. This article gives an overview of the complexity of psoriatic arthritis, looking at several aspects of this heterogeneous disease, such as epidemiology, important clinical features and comorbidities as well as current concepts of the pathophysiology and subsequent insights in novel treatment targets.

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Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2)

Abstract: PSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.

Cited by 140 publications

References 21 publications

Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

Inhibition of radiographic progression across levels of composite index-defined disease activity in patients with active psoriatic arthritis treated with intravenous golimumab: results from a phase-3, double-blind, placebo-controlled trial

An overview of psoriatic arthritis – epidemiology, clinical features, pathophysiology and novel treatment targets

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